Please use this identifier to cite or link to this item: doi:10.22028/D291-41511
Title: Differential Regulation of Circadian Clock Genes by UV-B Radiation and 1,25-Dihydroxyvitamin D: A Pilot Study during Different Stages of Skin Photocarcinogenesis
Author(s): Lamnis, Leandros
Christofi, Christoforos
Stark, Alexandra
Palm, Heike
Roemer, Klaus
Vogt, Thomas
Reichrath, Jörg
Language: English
Title: Nutrients
Volume: 16
Issue: 2
Publisher/Platform: MDPI
Year of Publication: 2024
Free key words: circadian clock
circadian rhythmicity
vitamin D
vitamin D signaling
vitamin D receptor
vitamin D receptor signaling
skin photocarcinogenesis
skin cancer
ultraviolet radiation
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: Background: Increasing evidence points at an important physiological role of the timekeeping system, known as the circadian clock (CC), regulating not only our sleep–awake rhythm but additionally many other cellular processes in peripheral tissues. It was shown in various cell types that environmental stressors, including ultraviolet B radiation (UV-B), modulate the expression of genes that regulate the CC (CCGs) and that these CCGs modulate susceptibility for UV-B-induced cellular damage. It was the aim of this pilot study to gain further insights into the CCs’ putative role for UV-B-induced photocarcinogenesis of skin cancer. Methods: Applying RT-PCR, we analyzed the expression of two core CCGs (brain and muscle ARNT-like 1 (Bmal1) and Period-2 (Per2)) over several time points (0–60 h) in HaCaT cells with and without 1,25-dihydroxyvitamin D (D3 ) and/or UV-B and conducted a cosinor analysis to evaluate the effects of those conditions on the circadian rhythm and an extended mixed-effects linear modeling to account for both fixed effects of experimental conditions and random inter-individual variability. Next, we investigated the expression of these two genes in keratinocytes representing different stages of skin photocarcinogenesis, comparing normal (Normal Human Epidermal Keratinocytes—NHEK; p53 wild type), precancerous (HaCaT keratinocytes; mutated p53 status), and malignant (Squamous Cell Carcinoma SCL-1; p53 null status) keratinocytes after 12 h under the same conditions. Results: We demonstrated that in HaCaT cells, Bmal1 showed a robust circadian rhythm, while the evidence for Per2 was limited. Overall expression of both genes, but especially for Bmal1, was increased following UV-B treatment, while Per2 showed a suppressed overall expression following D3 . Both UVB and 1,25(OH)2D3 suggested a significant phase shift for Bmal1 (p < 0.05 for the acrophase), while no specific effect on the amplitude could be evidenced. Differential effects on the expression of BMAL1 and Per2 were found when we compared different treatment modalities (UV-B and/or D3 ) or cell types (NHEK, HaCaT, and SCL-1 cells). Conclusions: Comparing epidermal keratinocytes representing different stages of skin photocarcinogenesis, we provide further evidence for an independently operating timekeeping system in human skin, which is regulated by UV-B and disturbed during skin photocarcinogenesis. Our finding that this pattern of circadian rhythm was differentially altered by treatment with UV-B, as compared with treatment with D3 , does not support the hypothesis that the expression of these CCGs may be regulated via UV-B-induced synthesis of vitamin D but might be introducing a novel photoprotective property of vitamin D through the circadian clock.
DOI of the first publication: 10.3390/nu16020254
URL of the first publication:
Link to this record: urn:nbn:de:bsz:291--ds-415119
ISSN: 2072-6643
Date of registration: 29-Jan-2024
Description of the related object: Supplementary Materials
Related object:
Faculty: M - Medizinische Fakultät
Department: M - Dermatologie
M - Innere Medizin
Professorship: M - Prof. Dr. Thomas Vogt
M - Keiner Professur zugeordnet
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

Files for this record:
File Description SizeFormat 
nutrients-16-00254.pdf1,44 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons